Description: This core is located at the Bedford VAMC. The specific aims of the core are as follows: 1) to facilitate the accomplishment of the scientific aims of the four projects by providing expertise in quantitative structural techniques and other technical support as needed;. 2) to perform detailed neuropathological examination of the brains and spinal cords of subjects studied in project 1, including unbiased cell counts on relevant brain regions, histological definition of oxidative injury, and the distribution of relevant proteins, including tau isoforms, alpha synuclein and ubiquitin; 3) to collaborate with project 2 by performing histological studies of oxidative markers and apoptosis on transgenic animal models; 4) to perform detailed histological examination on mice given intramuscular injections of TTC-GPT conjugate in project 4 to determine the extent of neuroprotection and to define the distribution of TTC and GPT in the spinal cords of treated animals; 5) to collaborate with project 3 by providing well characterized postmortem human tissue (AD, controls and other neurological diseases) and quantitating the distribution of abnormal EAA transporter transcripts in tissue using in situ hybridization. Specific methods include unbiased cell counting (stereology) and 3-D serial reconstruction of lesions, immunocytochemistry and in situ hybridization. Fifty-six autopsies have been performed at Bedford in the past year, with an autopsy rate of over 80 percent. A range of both fixed and deep-frozen tissue samples are acquired and stored using uniform acquisition procedures to ensure accuracy and reproducibility and fulfill the specific requirements of affiliated investigators. A comprehensive database is maintained on the brains of patients enrolled in the 100-bed Bedford Dementia Study Units to facilitate clinical-pathological correlative studies of the neurochemical, histological and neuropsychiatric aspects of neurodegenerative diseases including AD, PD, HD and ALS. Comprehensive facilities are currently available in this laboratory to perform the detailed quantitative histology and neuropathology in a consistent manner.